tbuckley/cabot-search huggingface dataset:
The evolving role of investigative toxicology in the pharmaceutical industry
Authors: Francois Pognan, Mario Beilmann, Harrie C. M. Boonen, Andreas Czich, Gordon Dear, Philip Hewitt, Tomas Mow, Teija Oinonen, Adrian Roth, Thomas Steger-Hartmann, Jean-Pierre Valentin, Freddy Van Goethem, Richard J. Weaver, Peter Newham
Journal: Nature Reviews Drug Discovery (2023)

For decades, preclinical toxicology was essentially a descriptive discipline in which treatment-related effects were carefully reported and used as a basis to calculate safety margins for drug candidates. In recent years, however, technological advances have increasingly enabled researchers to gain insights into toxicity mechanisms, supporting greater understanding of species relevance and translatability to humans, prediction of safety events, mitigation of side effects and development of safety biomarkers. Consequently, investigative (or mechanistic) toxicology has been gaining momentum and is now a key capability in the pharmaceutical industry. Here, we provide an overview of the current status of the field using case studies and discuss the potential impact of ongoing technological developments, based on a survey of investigative toxicologists from 14 European-based medium-sized to large pharmaceutical companies. Investigative toxicology tools and strategies are used in pharmaceutical companies to reduce safety-related attrition in drug development. This Perspective article summarizes the key goals of investigative toxicology, highlights current approaches and discusses selected emerging technologies that have the potential to improve the current safety-testing paradigm.
Nivolumab and Relatlimab in Patients With Advanced Melanoma That Had Progressed on Anti–Programmed Death-1/Programmed Death Ligand 1 Therapy: Results From the Phase I/IIa RELATIVITY-020 Trial
Authors: Paolo Antonio Ascierto, Evan J. Lipson, Reinhard Dummer, James Larkin, Georgina V. Long, Rachel E. Sanborn, Vanna Chiarion-Sileni, Brigitte Dréno, Stéphane Dalle, Dirk Schadendorf, Margaret K. Callahan, Marta Nyakas, Victoria Atkinson, Carlos Alberto Gomez-Roca, Naoya Yamazaki, Hussein A. Tawbi, Naomey Sarkis, Deepti Warad, Sonia Dolfi, Priyam Mitra, Satyendra Suryawanshi, Jean-Jacques Grob
Journal: Journal of Clinical Oncology (2023)

Nivolumab and relatlimab activity in advanced melanoma with prior progression on anti-programmed death-1/programmed death ligand 1 (PD-(L)1)-containing regimens is under investigation. RELATIVITY-047 demonstrated significantly improved progression-free survival (PFS) for nivolumab and relatlimab over nivolumab in previously untreated advanced melanoma.The phase I/IIa, open-label RELATIVITY-020 trial part D assessed efficacy and safety of nivolumab and relatlimab in advanced melanoma with progression during, or within 3 months of, 1 (D1) or ≥ 1 (D2) anti-PD-(L)1-containing regimens. Safety was a primary end point. Objective response rate (coprimary end point) and PFS by blinded independent central review (BICR) were assessed.Five hundred eighteen patients (D1 = 354; D2 = 164) received nivolumab and relatlimab. Among evaluable patients, the objective response rate by BICR was 12.0% (95% CI, 8.8 to 15.8) in D1 (n = 351) and 9.2% (95% CI, 5.2 to 14.7) in D2 (n = 163). Responses appeared to be enriched among patients with tumors expressing programmed death ligand 1 or lymphocyte activation gene 3; however, responses were observed regardless of programmed death ligand 1 and lymphocyte activation gene 3 expression (1%). The median duration of response was not reached (95% CI, 12.9 to not reached) in D1 and 12.8 months (95% CI, 6.9 to 12.9) in D2. The median PFS by BICR was 2.1 months (95% CI, 1.9 to 3.5) in D1 and 3.2 months (95% CI, 1.9 to 3.6) in D2; the 6-month PFS rate was 29.1% (95% CI, 24.2 to 34.1) and 27.7% (95% CI, 20.5 to 35.4), respectively. The grade 3-4 treatment-related adverse event incidence was 15.0% in D1 and 12.8% in D2. One case of grade 3 myocarditis and no treatment-related deaths occurred across part D.Nivolumab and relatlimab had a manageable safety profile and demonstrated durable clinical activity in a proportion of patients with heavily pretreated advanced melanoma with prior progression on anti-PD-(L)1-containing regimens.[Media: see text].
Cognitive Problems in Older Breast Cancer Survivors
Authors: Shijie Yang, Meijuan Tan, Feng Gao, Xiequn Xu
Journal: Journal of Clinical Oncology (2023)

The cognitive dysfunction of the brain, especially memory and attention, that occurs in older patients with breast cancer after treatment is one of the most concerning long-term symptoms.As a chronic inflammatory signal risk indicator for cardiovascular disease and death, C-reactive protein (CRP) has been suggested by several previous studies to correlate with cognitive problems in patients with cancer.In a recent article published in the Journal of Clinical Oncology, the authors evaluated the role of CRP on long-term cognitive problems in patients with cancer by examining CRP levels and cognitive problems in elderly patients with breast cancer and noncancer controls over a 60-month longitudinal period. 1 Here, we raise several concerns.
Annals Graphic Medicine - Banking Blood
Authors: Michael J. Green, Molly Osborne, Kimberly R. Myers, Zoe S. Schein
Journal: Annals of Internal Medicine (2023)

Web ExclusivesFebruary 2023Annals Graphic Medicine - Banking BloodFREEMichael J. Green, MD, MS, Molly Osborne, MD, PhD, Kimberly R. Myers, PhD, MA, and Zoe S. Schein, MAMichael J. Green, MD, MSPenn State College of Medicine, Hershey, Pennsylvania (M.J.G., K.R.M.)Search for more papers by this author, Molly Osborne, MD, PhDVA Portland Health Care System, Portland, Oregon (M.O.)Search for more papers by this author, Kimberly R. Myers, PhD, MAPenn State College of Medicine, Hershey, Pennsylvania (M.J.G., K.R.M.)Search for more papers by this author, and Zoe S. Schein, MARoslindale, Massachusetts (Z.S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0029 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Penn State College of Medicine, Hershey, Pennsylvania (M.J.G., K.R.M.)VA Portland Health Care System, Portland, Oregon (M.O.)Roslindale, Massachusetts (Z.S.S.)Acknowledgment: The authors would like to thank Dr. Evelyn M. Potochny, Assistant Medical Director of the Penn State Health Milton S. Hershey Medical Center Blood Bank, for her input on current protocols and practices.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0029.Author/Illustrator Information: Michael J. Green, MD, MS, is co-director of the Graphic Medicine International Collective and a professor in the Departments of Medicine and Humanities at Penn State College of Medicine (e-mail, [email protected]edu). Molly Osborne, MD, PhD, is Professor Emerita, Oregon Health & Science University, and Integrated Ethics Program Officer at Portland VA Medical Center (VAPORHCS) (e-mail, molly.[email protected]gov). Kimberly R. Myers, PhD, MA, is Professor of Humanities and Medicine at Penn State College of Medicine and author/editor of six books, including Clinical Ethics: A Graphic Medicine Casebook (e-mail, [email protected]edu). Zoe S. Schein, MA, Rhode Island School of Design (RISD), is a freelance illustrator and teacher (e-mail, [email protected]com).This article was published at Annals.org on 14 February 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics February 2023Volume 176, Issue 2 ePublished: 14 February 2023 Issue Published: February 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
How Would You Resuscitate This Patient With Septic Shock?
Authors: Zahir Kanjee, Katherine Berg, Taison D. Bell, Eileen E. Reynolds
Journal: Annals of Internal Medicine (2023)

Sepsis is a potentially life-threatening systemic dysregulatory response to infection, and septic shock occurs when sepsis leads to systemic vasodilation and subsequent tissue hypoperfusion. The Surviving Sepsis Campaign published updated guidelines in 2021 on the management of sepsis and septic shock. Here, in the context of a patient with septic shock, 2 critical care specialists discuss and debate conditional guideline recommendations on using lactate to guide resuscitation, the use of balanced crystalloids versus normal saline, and the use of corticosteroids.
The role of aldehyde dehydrogenase 2 in cardiovascular disease
Authors: Jian Zhang, Yunyun Guo, Xiangkai Zhao, Jiaojiao Pang, Chang Pan, Jiali Wang, Shujian Wei, Xiao Yu, Cheng Zhang, Yuguo Chen, Huiyong Yin, Feng Xu
Journal: Nature Reviews Cardiology (2023)
US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer
Authors: Preeti Narayan, Asma Dilawari, Christy Osgood, Zhou Feng, Erik Bloomquist, William F. Pierce, Samina Jafri, Shyam Kalavar, Marina Kondratovich, Prakash Jha, Soma Ghosh, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Laleh Amiri-Kordestani
Journal: Journal of Clinical Oncology (2023)

PURPOSE The US Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd) for the treatment of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry 1 + or immunohistochemistry 2+/in situ hybridization–) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. PATIENTS AND METHODS Approval was based on DESTINY-Breast04, a phase III, randomized, open-label, multicenter trial in patients with unresectable or metastatic HER2-low breast cancer, determined at a central laboratory. A total of 557 patients were randomly assigned (2:1) to receive either T-DXd 5.4 mg/kg intravenously once every 3 weeks (n = 373) or physicians' choice of chemotherapy (n = 184). RESULTS The study met its primary efficacy end point of progression-free survival (PFS) by blinded independent central review assessment in the hormone receptor–positive (HR+) cohort (N = 494) with an estimated hazard ratio (HR) of 0.51(95% CI, 0.40 to 0.64; P &lt; .0001). Key secondary end points were also met, including PFS in the intent-to-treat population with an HR of 0.50 (95% CI, 0.40 to 0.63; P &lt; .0001), overall survival (OS) in the HR+ cohort with an HR of 0.64 (95% CI, 0.48 to 0.86; P = .0028) and OS in the intent-to-treat with an HR of 0.64 (95% CI, 0.49 to 0.84; P = .0010). The safety profile of T-DXd was consistent with previously approved indications, and no new safety signals were observed in this study population. CONCLUSION The approval of T-DXd in HER2-low metastatic breast cancer was based on statistically significant and clinically meaningful PFS and OS improvements observed in the DESTINY-Breast04 trial and represents the first approved therapy specifically for the treatment of HER2-low metastatic breast cancer.
Circulating tumour DNA analysis predicts relapse and improves risk stratification in primary refractory multiple myeloma
Authors: Sridurga Mithraprabhu, John Reynolds, Rose Turner, Hang Quach, Noemi Horvath, Ian Kerridge, Anna Kalff, Krystal Bergin, Jay Hocking, Flora Yuen, Tiffany Khong, Brian M. Durie, Andrew Spencer
Journal: Blood Cancer Journal (2023)
PCSK6 and Survival in Idiopathic Pulmonary Fibrosis
Authors: Justin M. Oldham, Richard J. Allen, Jose M. Lorenzo-Salazar, Philip L. Molyneaux, Shwu-Fan Ma, Chitra Joseph, John S. Kim, Beatriz Guillen-Guio, Tamara Hernández-Beeftink, Jonathan A. Kropski, Yong Huang, Cathryn T. Lee, Ayodeji Adegunsoye, Janelle Vu Pugashetti, Angela L. Linderholm, Vivian Vo, Mary E. Strek, Jonathan Jou, Adrian Muñoz-Barrera, Luis A. Rubio-Rodriguez, Richard Hubbard, Nik Hirani, Moira K. B. Whyte, Simon Hart, Andrew G. Nicholson, Lisa Lancaster, Helen Parfrey, Doris Rassl, William Wallace, Eleanor Valenzi, Yingze Zhang, Josyf Mychaleckyj, Amy Stockwell, Naftali Kaminski, Paul J. Wolters, Maria Molina-Molina, Nicholas E. Banovich, William A. Fahy, Fernando J. Martinez, Ian P. Hall, Martin D. Tobin, Toby M. Maher, Timothy S. Blackwell, Brian L. Yaspan, R. Gisli Jenkins, Carlos Flores, Louise V. Wain, Imre Noth
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers of IPF progression is needed.
Multifunctional Scaffold for Osteoporotic Pathophysiological Microenvironment Improvement and Vascularized Bone Defect Regeneration
Authors: Yanan Zhao, Honglei Kang, Xiaopei Wu, Pengzhen Zhuang, Rong Tu, Takashi Goto, Feng Li, Honglian Dai
Journal: Advanced Healthcare Materials (2023)

Abstract Osteoporosis is a degenerative bone disease resulting from bone homeostasis imbalance regulated by osteoblasts and osteoclasts. Treating osteoporotic bone defects tends to be more difficult due to suppressed osteogenic differentiation, hyperactive osteoclastogenesis, and impaired angiogenesis. Hence, a drug carrier system composed of gelatin‐coated hollow mesoporous silica nanoparticles (HMSNs/GM) loaded with pro‐osteogenic parathyroid (PTH) and anti‐osteoclastogenic alendronate (ALN) is constructed and compounded into calcium magnesium phosphate cement (MCPC). The spatial‐temporal release of ions and drugs, controllable degradation rate, and abundant pore structure of MCPC composites enhance osteoporotic bone regeneration in ovariectomized rats by accelerating vascularization, promoting osteogenic differentiation and mineralization, and inhibiting osteoclastogenesis and bone resorption. The MCPC/HMSNs@ALN‐PTH/GM demonstrates a synergistic threefold effect on osteogenesis, osteoclastogenesis, and angiogenesis. It improves the osteoporotic pathophysiological microenvironment and promotes osteoporotic vascularized bone defect regeneration, holding huge potential for other functional biomaterials design and clinical management.
Bridging biological cfDNA features and machine learning approaches
Authors: Tina Moser, Stefan Kühberger, Isaac Lazzeri, Georgios Vlachos, Ellen Heitzer
Journal: Trends in Genetics (2023)

Liquid biopsies (LBs), particularly using circulating tumor DNA (ctDNA), are expected to revolutionize precision oncology and blood-based cancer screening. Recent technological improvements, in combination with the ever-growing understanding of cell-free DNA (cfDNA) biology, are enabling the detection of tumor-specific changes with extremely high resolution and new analysis concepts beyond genetic alterations, including methylomics, fragmentomics, and nucleosomics. The interrogation of a large number of markers and the high complexity of data render traditional correlation methods insufficient. In this regard, machine learning (ML) algorithms are increasingly being used to decipher disease- and tissue-specific signals from cfDNA. Here, we review recent insights into biological ctDNA features and how these are incorporated into sophisticated ML applications.
Chagas Disease
Authors: Natasha S. Hochberg, Susan P. Montgomery
Journal: Annals of Internal Medicine (2023)

Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi, is a leading neglected tropical disease in the United States. An estimated 240 000 to 350 000 persons in the United States are infected, primarily immigrants from Mexico, Central America, and South America, where the disease is endemic. The parasite is transmitted by the triatomine bug but can also be passed through blood transfusion, via organ transplant, or congenitally. Approximately 30% of infected persons later develop cardiac and/or gastrointestinal complications. Health care providers should consider screening at-risk patients with serologic testing. Early diagnosis and treatment with benznidazole or nifurtimox can help prevent complications.
Overcoming disparities for sexual and gender minority patients and providers in gastroenterology and hepatology: introduction to Rainbows in Gastro
Authors: Nikki Duong, Tzu-Hao Lee, Kira L Newman, Alexander Goldowsky, Kara J Jencks, Victor Chedid, Jasmine Barrow, Rebecca Burbridge, Austin Chiang, Laura Targownik, Douglas A Simonetto, Sonali Paul
Journal: The Lancet. Gastroenterology & hepatology (2023)
Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis
Authors: Hisham Mehanna, Miren Taberna, Christian von Buchwald, Sara Tous, Jill Brooks, Marisa Mena, Francisca Morey, Christian Grønhøj, Jacob Høygaard Rasmussen, Martin Garset-Zamani, Laia Bruni, Nikolaos Batis, Ruud H Brakenhoff, C René Leemans, Robert J Baatenburg de Jong, Jens Peter Klussmann, Nora Wuerdemann, Steffen Wagner, Tina Dalianis, Linda Marklund, Haïtham Mirghani, Andrew Schache, Jaqueline A James, Shao Hui Huang, Brian O'Sullivan, Paul Nankivell, Martina A Broglie, Markus Hoffmann, Elgar Susanne Quabius, Laia Alemany, Hisham Mehanna, Miren Taberna, Christian von Buchwald, Sara Tous, Shao Hui Huang, Brian O'Sullivan, Martin Garset-Zamani, Jill Brooks, Nikolaos Batis, Tessa Fulton-Lieuw, Paul Nankivell, Andrew Schache, Jacqueline A James, Ruud H Brakenhoff, C Rene Leemans, Danielle AM Heideman, Elisabeth Bloemena, Irene Nauta, Robert Baatenburg de Jong, Tina Dalianis, Linda Marklund, Haïtham Mirghani, Steffen Wagner, Claus Wittekindt, Jens Peter Klussmann, Nora Wuerdemann, Alexander Quaas, Shachi Jenny Sharma, Margaret Maltseva, Philipp Zimmermann, Markus Hoffmann, Elgar Susanne Quabius, Martina Broglie Däppen, Leitende Ärztin, Laia Bruni, Marisa Mena, Francisca Morey, Laia Alemany
Journal: The Lancet Oncology (2023)
The Use of Opioids in the Management of Chronic Pain: Synopsis of the 2022 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline
Authors: Friedhelm Sandbrink, Jennifer L. Murphy, Melanie Johansson, Juli L. Olson, Ellen Edens, Jamie Clinton-Lont, James Sall, Christopher Spevak, Friedhelm Sandbrink, Jennifer L. Murphy, Melanie Johansson, Christopher Spevak, Jamie Clinton-Lont, Ellen Edens MD, Juli L. Olson, Nicole Brown, Raquel Guinta, Franz Macedo, Mitchell Nazario, Sanjog Pangarkar, Samuel Preston, Matthew Prince, Donna Endsley Real, David Riegleman, Evan Steil, ECRI Institute, Lewin Group, Sigma Health Consulting
Journal: Annals of Internal Medicine (2023)

In May 2022, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the use of opioids when managing chronic pain. This synopsis summarizes the recommendations that the authors believe are the most important to highlight.In December 2020, the VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2017 VA/DoD Clinical Practice Guideline for Opioid Therapy for Chronic Pain. The guideline development team included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy clinical practice guidelines. The guideline team developed key questions to guide a systematic evidence review that was done by an independent third party and distilled 20 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The guideline team also created 3 one-page algorithms to help guide clinical decision making. This synopsis presents the recommendations and highlights selected recommendations on the basis of clinical relevance.This guideline is intended for clinicians who may be considering opioid therapy to manage patients with chronic pain. This synopsis reviews updated recommendations for the initiation and continuation of opioid therapy; dose, duration, and taper of opioids; screening, assessment, and evaluation; and risk mitigation. New additions are highlighted, including recommendations about the use of buprenorphine instead of full agonist opioids; assessing for behavioral health conditions and factors associated with higher risk for harm, such as pain catastrophizing; and the use of pain and opioid education to reduce the risk for prolonged opioid use for postsurgical pain.
Temporary treatment cessation versus continuation of first-line tyrosine kinase inhibitor in patients with advanced clear cell renal cell carcinoma (STAR): an open-label, non-inferiority, randomised, controlled, phase 2/3 trial
Authors: Janet E Brown, Kara-Louise Royle, Walter Gregory, Christy Ralph, Anthony Maraveyas, Omar Din, Timothy Eisen, Paul Nathan, Tom Powles, Richard Griffiths, Robert Jones, Naveen Vasudev, Matthew Wheater, Abdel Hamid, Tom Waddell, Rhona McMenemin, Poulam Patel, James Larkin, Guy Faust, Adam Martin, Jayne Swain, Janine Bestall, Christopher McCabe, David Meads, Vicky Goh, Tze Min Wah, Julia Brown, Jenny Hewison, Peter Selby, Fiona Collinson, Judith Carser, Gopalakrishnan Srinivasan, Fiona Thistlewaite, Ashraf Azzabi, Mark Beresford, David Farrugia, Marios Decatris, Carys Thomas, Joanna Gale, James McAleer, Alison Clayton, Ekaterini Boleti, Thomas Geldart, Santhanam Sundar, Jason Lester, Nachi Palaniappan, Mohan Hingorani, Khaliq Rehman, Mohammad Khan, Naveed Sarwar, Janine Graham, Alastair Thomson, Narayanan Srihari, Denise Sheehan, Rajaguru Srinivasan, Omar Khan, Andrew Stockdale Jane Worlding, Stergios Boussios, Nicholas Stuart, Carey MacDonald-Smith, Falalu Danwata, Duncan McLaren, Aravindhan Sundaramurthy, Anna Lydon, Sharon Beesley, Kathryn Lees, Mohini Varughese, Emma Gray, Angela Scott, Mark Baxter, Anna Mullard, Pasquale Innominato, Gaurav Kapur, Anil Kumar, Natalie Charnley, Caroline Manetta, Prabir Chakraborti, Prantik Das, Sarah Rudman, Henry Taylor, Christos Mikropoulos, Martin Highley, Dakshinamoorthy Muthukumar, Anjali Zarkar, Roy Vergis, Seshadri Sriprasad, Patryk Brulinski, Amanda Clarke, Richard Osbourne, Melanie Harvey, Renata Dega, Geoffrey Sparrow, Urmila Barthakur, Erica Beaumont, Caroline Manetta, Agnieszka Michael, Emilio Porfiri, Faisal Azam, Ravi Kodavtiganti
Journal: The Lancet Oncology (2023)
Circadian disruption and sleep disorders in neurodegeneration
Authors: Yun Shen, Qian-kun Lv, Wei-ye Xie, Si-yi Gong, Sheng Zhuang, Jun-yi Liu, Cheng-jie Mao, Chun-feng Liu
Journal: Translational Neurodegeneration (2023)

Abstract Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases. Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep. Importantly, circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases. Thus, harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine. In this review, we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies, focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration. These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.